Mechanosensitive cGMP signalling in platelets (A05)

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The cyclic nucleotide cGMP is an important signalling molecule of our cardiovascular system and increasingly targeted by clinically used drugs. We have discovered a mechanosensitive cGMP pathway (mechano-cGMP) in mouse and human platelets that is organised by a membrane-associated integrin-cGMP signalosome. In this project, we will study the molecular architecture and mode of action of mechano-cGMP as well as its functional and therapeutic relevance in mouse and human. We hypothesise that the novel link between integrin and cGMP signalling provides a flow/shear-sensitive break mechanism to prevent platelet overactivity in platelet-related disorders.